There is no uniform Persistent, Bioaccumulative, Toxic (PBT) or very Persistent, very Bioaccumulative (vPvB) assessment of chemicals in Europe, as the various regulatory frameworks use only limited or dissimilar PBT assessments, or none at all. The European REACH Regulation requires a PBT/vPvB assessment for all chemical substances that are produced within or imported into the EU in amounts exceeding 10 tonnes per year, using the criteria as described in REACH Annex XIII. However, not all substances on the EU market need to be screened according to these criteria under REACH. For a number of substances, such as those imported or produced in lower volumes, there is no REACH requirement, and for human and veterinary medicinal products, biocides, plant protection products, and food and feed additives, other EU legislation is in force to regulate their marketing and use. Compounds may also be screened for PBT properties within international agreements, such as the Oslo Paris Convention (OSPAR), the IMO Ballast Water Management Convention, the UNECE POP Protocol, and the UNEP Stockholm Convention on Persistent Organic Pollutants (POPs), which all have their own set of PBT or POP criteria. This study compares the PBT/vPvB assessment under REACH with PBT or POP assessments performed within other regulatory frameworks. Attention is paid to the process of PBT/vPvB/POP identification and which legislative steps can be taken if the PBT/vPvB/POP status is assigned. In addition to the different PBT or POP criteria of the various frameworks, descriptions of these criteria and approaches for application of weight of evidence also vary. Some EU frameworks still refer to the criteria in the former Technical Guidance Documents (TGD) of 2003, which preceded REACH. Although differences between the old TGD criteria and those in the REACH Annex XIII are small, this does cause dissimilarities among the frameworks. The risk management follow-up of a PBT or vPvB identification, which may include a socio economic analysis, also depends on the legal framework and the specific conditions under which a substance is used. Irrespective of the framework in which a substance is used, individual European Member States may propose a substance evaluation for PBT or vPvB identification under REACH. However, authorization is only possible for uses of PBT substances that are not covered by their regular framework but are registered under REACH. How socio-economic criteria should be weighed against PBT/vPvB properties and environmental risks in authorizing or restricting the use of PBT/vPvB substances is often not specified. Thus, although the goal of restricting or banning the use of PBT/vPvB substances is shared among all EU-based regulatory frameworks, there are many differences in how to achieve this goal. These differences create a challenge to harmonize the PBT/vPvB assessment of substances, not only regarding technical criteria, but also regarding regulatory follow-up.